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Background: The efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2- negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States. Methods: We performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Results: SG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be costeffective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY. Conclusion: From a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The costeffectiveness of SG can be improved if the price is substantially reduced. [ABSTRACT FROM AUTHOR]

Background: In patients with advanced non-small cell lung cancer (aNSCLC), cemiplimab plus chemotherapy prolonged overall survival (OS) and progressionfree survival (PFS) significantly compared to chemotherapy alone. The costeffectiveness of these drugs is still uncertain. The aim of this study is to assess the cost-effectiveness of cemiplimab plus chemotherapy compared with chemotherapy for the treatment of aNSCLC from the third-party payer perspective in the United States. Materials and methods: The cost-effectiveness of cemiplimab with chemotherapy versus chemotherapy for the treatment of aNSCLC was evaluated using a partitioned survival model containing three mutually incompatible health states. The clinical characteristics and outcomes used in the model were gathered from EMPOWER-Lung 3 trial. We have conducted deterministic one-way sensitivity analysis and probabilistic sensitivity analysis in order to evaluate the robustness of the model. The primary outcomes considered were the costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB). Results: Treatment of aNSCLC with cemiplimab plus chemotherapy increased efficacy by 0.237 QALYs and was associated with an increased total cost of $50,796 compared to chemotherapy alone, resulting in an ICER of $214,256/QALY gained. At a WTP threshold of $150,000/QALY, the INHB of cemiplimab plus chemotherapy was 0.203 QALYs and the INMB was $304,704 compared to chemotherapy alone. The probabilistic sensitivity analysis revealed that there was only a 0.04% chance that cemiplimab with chemotherapy would be costeffective at a WTP threshold of $150,000/QALY. The performance of model was mainly determined by the price of cemiplimab, according to a one-way sensitivity analysis. Conclusions: From the third-party payer perspective, cemiplimab combined chemotherapy is unlikely to be a cost-effective option for the treatment of aNSCLC at the WTP threshold of $150,000/QALY in the United States. [ABSTRACT FROM AUTHOR]

Objective: Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC. Materials and methods: A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured. Results: The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was $220,864/QALY. The INHB and INMB were -0.15 QALYs and -$22,362 at a willingness-to-pay (WTP) threshold of $150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded $0.93/mg or nivolumab was less than $24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of costeffectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of $150,000/QALY. This study also showed that the probability of cost-effectiveness was <50% in most subgroups. Conclusion: Nivolumab was not cost-effective, although it was associated with better clinical benefit and a favorable safety profile for the treatment of aHCC compared with sorafenib from the third-party payer perspective in the United States. If the price of nivolumab is substantially reduced, favorable cost-effectiveness can be achieved among patients with aHCC. [ABSTRACT FROM AUTHOR]

The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures. [ABSTRACT FROM AUTHOR]

The incidence of involved intramammary lymph node (intra‐MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra‐MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T‐stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow‐up. Stage 4 cases and/or neo‐adjuvant treated patients were excluded. AJCC TN‐stage was calculated twice, with and without intra‐MLN. Five‐year overall survival (OS) and relapse (local and/or distant)‐free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra‐MLN, TN‐stage correlated with OS (P =.016) but not with RFS (P =.19). However, when intra‐MLN was included, TN‐stage correlated with both OS (P <.001) and RFS (P =.016). In the multivariate analysis, when intra‐MLN was excluded, only radiation therapy (RT) correlated with RFS (HR = 0.19, 95% CI: 0.054‐0.66, P =.009). However, when intra‐MLN was included in the TN‐stage both RT (HR = 0.13, 95% CI: 0.04‐0.45, P =.001) and TN‐stage 3 (HR = 8.92, 95% CI: 1.47‐54, P =.017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra‐MLN involvement was excluded. When intra‐MLN was included, multifocality became insignificant but TN‐stage 3 correlated with OS (HR = 8.59, 95% CI: 1.06‐69.71, P =.044). Positive intra‐MLN is an independent factor in predicting both RFS and OS. [ABSTRACT FROM AUTHOR]

In this paper, we derived a high-efficiency formula for calculating the precision of carrier phase relative positioning, analyzed the various factors that affect the positioning accuracy using the carrier phase, and proposed the concept of using a frequency dilution of precision to describe the quantitative effect of different frequency combinations on the positioning precision. To this end, we computed and plotted the global spatial distribution map of the relative positioning dilution of precision for single-day solution, half-hour solution, and single-epoch solution of the global positioning system (GPS), regional Beidou navigation satellite system (BDS2), future global Beidou navigation satellite system (BDS3), and their fusion systems. Using processing software with autonomous intellectual property rights (GCN and VENUS/ARSNet), we solved the measurement data and examined the positioning precision of the single-day solution and single-epoch solution of GPS and BDS2. The analysis demonstrated that the B1/B2 frequency positioning precision of BDS2 was better than that of L1/L2 frequency positioning of GPS, but the positioning precision of the BDS2 is worse than that of GPS over most of the service region of the BDS2. Further, the positioning precision of BDS3 is better than that of GPS in the Asia-Pacific region, while it is the opposite in other regions. Based on these conclusions, we put forth some optimization recommendations regarding the signal frequency of the navigation system and GPS measurement standards to serve as references for optimizing the system performance and formulating standards. [ABSTRACT FROM AUTHOR]

In the United States, steps to advance health equity often take place at the state and local levels rather than the national level. Using publicly available data sources, we developed a scorecard for all fifty states and the District of Columbia that measures indicators of the use of five evidence-based policies to address domains related to health equity. The indicators are the cigarette excise tax rate, a state's Medicaid expansion status and the size of its coverage gap, percentage of four-year olds enrolled in state-funded pre-kindergarten, minimum wage level, and the presence of state-funded housing subsidy programs and homelessness prevention and rapid rehousing programs. We found that states varied significantly in their implementation of the selected policies and concluded that a variety of approaches to encourage policy changes at the state level will be needed to create healthier and more equitable communities. We describe promising, feasible state-level approaches for states to "do something, do more, do better" when they take action on the five selected policies that can promote health equity. [ABSTRACT FROM AUTHOR]

The article discusses issues of psychological disorders, suicidal ideation, and substance abuse within law students and legal professionals in the U.S., and discusses the partnership between the social sciences and the legal community along with Law School Stressor Measure for addressing same.

Li (2009) found that the association between fee dependence (FEEDEP) and the incidence of going-concern opinions (GCO) changed from insignificant in 2001 to positive in 2003. This finding has been interpreted as evidence that auditors became more conservative after the Sarbanes-Oxley Act (SOX). However, Feldmann and Read (2010) suggested that the year following SOX was not typical due to the intense spotlight directed at the audit profession. We revisit Li (2009) by extending the post-SOX period to 2011, and find robust results of little FEEDEP-GCO association in the years after 2003. Hence, the rise in auditor conservatism identified by Li (2009) likely represented the audit profession's temporary reaction to public scrutiny surrounding the passage of SOX, rather than a sustained movement toward more conservative going-concern reporting. Our study reinforces the notion that the effect of major events and government regulations cannot be adequately assessed based on what transpires in the short run. [ABSTRACT FROM AUTHOR]

The article examines the effects of using circle hooks on seabird bycatch in the U.S. Atlantic pelagic longline fishery. It mentions the use of generalized linear models to examine such condition. It notes that the probability of catching seabirds is influenced by the combinations of hook type and size. It also emphasizes that the effectiveness of using circle hook is confounded by bait type, fishing location, and season.

Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock. [ABSTRACT FROM AUTHOR]

Human sera from the United States, Thailand, and sub-Saharan Africa and chimpanzee sera were tested for neutralizing antibodies to 3 chimpanzee adenoviruses. Antibodies were more common in humans residing in sub-Saharan Africa than in humans living in the United States or Thailand. This finding suggests cross-species transmission of chimpanzee adenoviruses. [ABSTRACT FROM AUTHOR]

Discusses the feelings of racial oppression among Asian immigrants as illustrated in the books `Eat a Bowl of Tea,' by Louis Chu and `Crossing,' by Hua Chuang. Cultural domination by original country; Cultural differences in decision-making; Transformation of consciousness; Integration of one culture with another; Reaction to interracial marriage.

Background: Relatively little is known about the differences in prognostic factors for early vs late recurrence among women with early stage estrogen receptor-positive breast cancer., Methods: We analyzed factors related to early (<5 years) vs late (≥5 years) recurrence in 2992 women with stage I-IIB estrogen receptor-positive breast cancer in the Pathways Study, a prospective cohort of women with breast cancer enrolled between 2006 and 2013, with ascertainment of recurrence and death through December 2021., Results: After a median follow-up of 13.3 years, 341 (13.8%) women had recurrences, including 181 (53.7%) with late recurrence. Higher stage and grade were associated with recurrence regardless of timing, whereas progesterone receptor negativity was associated with early but not late recurrence. Receipt of endocrine therapy was associated with reduced risk of overall recurrence, but the length of endocrine therapy was not statistically significant in multivariable models. Minoritized racial and ethnic groups, including Asian, Black, and Hispanic women, had higher risk of early but not late recurrence compared to non-Hispanic White women. The trend of higher risk of early recurrence among these groups remained after adjustment for clinical, demographic, and socioeconomic factors but was statistically significant only in Asian women., Conclusions: Our study revealed potentially important distinctions for early vs late recurrence, including the associations with progesterone receptor negativity and self-identified race and ethnicity. Possible higher risk of early recurrence among Asian, Black, and Hispanic women provides novel evidence for the existence of disparities in cancer outcomes, even within the breast cancer subtype indicative of generally good prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nicotine is a known toxin, but its relationship with cervicovaginal high-risk human papillomavirus (HR-HPV) infection is uncertain. This study aimed to investigate whether tobacco exposure is associated with elevated cervicovaginal HR-HPV infection in US women, and if the strength of this association varies with the degree of exposure. Cross-sectional data from the 2011-2016 National Health and Nutrition Examination Survey (NHANES), which included a nationally representative sample of US women, were used for the study. Out of 12436 women aged 18-59 who participated in the interview, 3833 were ultimately enrolled in this study. Weighted logistic regression was used to estimate the link between tobacco exposure and cervicovaginal HR-HPV infection. The mean age of participants was 38.6 (SD 12.1) years, and non-Hispanic White individuals accounted for 37.3% of the sample. Those with any tobacco exposure tended to be younger (mean age 37.7 [SD 12.4] years vs 40.3 [11.2] years), non-Hispanic Black (27.8% vs. 15.1%), lower educated (41.8% vs. 29.4%), and have lower family income (39.9% vs. 23.5%). After adjustment, the odds of having HR-HPV infection were 1.32 (95% CI, 1.09-1.59) for those exposed to tobacco, remaining significant in multiple sensitivity analyses and across subgroups. This study, based on a nationally representative sample from the United States, suggests that tobacco exposure is a risk factor for elevated HR-HPV infection in women, highlighting the need for further research into reducing this modifiable risk factor., (© 2023. The Author(s).)

Importance: Spouses share common socioeconomic, environmental, and lifestyle factors, and multiple studies have found that spousal diabetes status was associated with diabetes prevalence. But the association of spousal diabetes status and ideal cardiovascular health metrics (ICVHMs) assessed by the American Heart Association's Life's Essential 8 measures with incident diabetes has not been comprehensively characterized, especially in large-scale cohort studies., Objective: To explore the association of spousal diabetes status and cardiovascular health metrics with risk of incident diabetes in Chinese adults., Design, Setting, and Participants: This cohort study included individuals in the China Cardiovascular Disease and Cancer Cohort without diabetes who underwent baseline and follow-up glucose measurements and had spouses with baseline glucose measurements. The data were collected in January 2011 to December 2012 and March 2014 to December 2016. The spousal study had a mean (SD) follow-up of 3.6 (0.9) years (median [IQR], 3.2 [2.9-4.5] years). Statistical analysis was performed from July to November 2022., Exposure: Spousal diabetes status was diagnosed according to the 2010 American Diabetes Association (ADA) criteria. All participants provided detailed clinical, sociodemographic, and lifestyle information included in cardiovascular health metrics., Main Outcomes and Measures: Incident diabetes, diagnosed according to 2010 ADA criteria., Results: Overall, 34 821 individuals were included, with a mean (SD) age of 56.4 (8.3) years and 16 699 (48.0%) male participants. Spousal diabetes diagnosis was associated with an increased risk of incident diabetes (hazard ratio [HR], 1.15; 95% CI, 1.03-1.30). Furthermore, participants whose spouses had uncontrolled glycated hemoglobin (HbA1c) had a higher risk of diabetes (HR, 1.20; 95% CI, 1.04-1.39) but the risk of diabetes in participants whose spouses had controlled HbA1c did not increase significantly (HR, 1.10; 95% CI, 0.92-1.30). Moreover, this association varied with composite cardiovascular health status. Diabetes risk in individuals who had poor cardiovascular health status (<4 ICVHMs) was associated with spousal diabetes status (3 ICVHMs: HR, 1.50; 95% CI, 1.15-1.97), while diabetes risk in individuals who had intermediate to ideal cardiovascular health status (≥4 ICVHMs) was not associated with it (4 ICVHMs: HR, 1.01; 95% CI, 0.69-1.50)., Conclusions and Relevance: In this study, spousal diabetes diagnosis with uncontrolled HbA1c level was associated with increased risk of incident diabetes, but strict management of spousal HbA1c level and improving ICVHM profiles may attenuate the association of spousal diabetes status with diabetes risk. These findings suggest the potential benefit of couple-based lifestyle or pharmaceutical interventions for diabetes.

Background: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD., Objective: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM)., Methods: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool., Results: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I 2 =80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I 2 =38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I 2 =63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall., Conclusions: Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

This article explores the ways East Asian American (EAA) children and adolescents have experienced disparities in the United States throughout the COVID-19 pandemic. The history of racism toward Asian American and Pacific Islanders (AAPI) and the complexities of acculturation are reflected through this contemporary lens. Traditional East Asian (EA) values were disrupted during this period. Implications for children and families are discussed. Persistent underlying xenophobia and racism, such as the model minority myth or perpetual foreigner stereotype, rose to new prominence, furthering emotional distress in EA and EAA youths beyond those already experienced universally by AAPI families during the pandemic., Competing Interests: Disclosure S. Chou reports no financial relationships or interests. C. Han reports no financial relationships or interests. J.X. Ouyang reports no financial relationships or interests. A.S. Li reports the following conflict of interest: chapter coauthor for Cultural Psychiatry in Children Adolescents and Families, American Psychiatric Publishing, 2021., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This article draws into focus the role of cultural and structural humility in shaping a mental health system that can address the mental health disparities for BIPOC youths. In an era of growing diversity in the United States population and a calling out of racism and discrimination on an interpersonal and systemic level, the commitment to a lifelong engagement of cultural awareness and an openness to reflect and critique, is whereby mutual partnerships between professionals, patients, and clinician themselves can strengthen. This hallmark tenet of cultural humility is actively being adopted into community programs and academic health care institutions as ways to improve the mental health understanding and needs of BIPOC youths., Competing Interests: Disclosure A.S. Li reports the following conflict of interest: chapter coauthor for Cultural Psychiatry in Children Adolescents and Families, American Psychiatric Publishing 2021. Q. Lang reports no financial relationships or interests. J. Cho reports the following conflict of interest: chapter coauthor for Cultural Psychiatry in Children Adolescents and Families, American Psychiatric Publishing 2021. V-S. Nguyen reports no financial relationships or interests. S. Nandakumar reports no financial relationships or interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for high blood pressure (BP) in adults came up with a new definition of hypertension with a threshold BP level of 130/80 mmHg. But the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines adhered to a conventional hypertension definition as BP ≥ 140/90 mmHg. We aimed to compare the trajectories of cognitive decline between participants with BP < 130/80 mmHg in all BP measurement waves and others with all BP < 140/90 mmHg., Methods: This pooled analysis involved middle-aged and older participants from three nationally representative ageing cohorts, including the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health Retirement Longitudinal Study (CHARLS). Participants were divided into the Normal (BP < 130/80 mmHg on all occasions throughout the study), the Borderline (BP < 140/90 mmHg on all occasions throughout the study but not in the Normal group), and the High (the rest of participants) BP groups. Global cognitive Z score was calculated from tests on memory, executive function, and orientation., Results: A total of 17,590 participants (HRS 6964, median follow-ups 12 years; ELSA 5334, median follow-ups 16 years; CHARLS 5292, median follow-ups 7 years) were included. No significant difference in global cognitive decline rate was detected between the Normal and the borderline groups (men, pooled β = - 0.006 standard deviation [SD]/year; 95% confidence interval [CI], - 0.020 to 0.008; P = 0.377; women, pooled β = 0.006 SD/year; 95% CI - 0.005 to 0.018; P = 0.269). Participants in the High group had a significantly faster cognitive decline (men, pooled β = - 0.011 SD/year; 95% CI - 0.020 to - 0.002; P = 0.013; women, pooled β = - 0.017 SD/year; 95% CI - 0.026 to - 0.008; P < 0.001) than that in the Borderline group., Conclusions: Individuals in the Borderline group did not experience significantly faster cognitive decline compared with those in the Normal group. It might not be necessary for individuals with borderline BP (between 130/80 and 140/90 mmHg) to initiate antihypertension therapy in consideration of cognitive decline., (© 2021. The Author(s).)

Importance: Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials., Objective: To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs., Design, Setting, and Participants: This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings., Interventions: Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up., Main Outcomes and Measures: The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs., Results: In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group., Conclusions and Relevance: In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months)., Trial Registration: ClinicalTrials.gov Identifier: NCT01898923.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension., Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017., Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years., Conclusion: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objectives. To assess stakeholder perceptions of the impact and feasibility of 21 national, state, and local nutrition policies for cancer prevention across 5 domains in the United States. Methods. We conducted an online survey from October through December 2018. Participants were invited to take the survey via direct e-mail contact or an organizational e-newsletter. Results. Federal or state Medicare/Medicaid coverage of nutrition counseling and federal or state subsidies on fruits, vegetables, and whole grains for participants in the Supplemental Nutrition Assistance Program were the policies rated as having the highest perceived impact and feasibility. Overall, the 170 respondents rated policy impact higher than policy feasibility. Polices at the federal or state level had a higher perceived impact, whereas local policies had higher perceived feasibility. Conclusions. Our findings might guide future research and advocacy that can ultimately motivate and target policy actions to reduce cancer burdens and disparities in the United States.

The incidence rate of hepatocellular carcinoma (HCC) is higher in populations of Asian ancestry than European ancestry (EA). We sought to investigate HCC mutational differences between the two populations, which may reflect differences in the prevalence of etiological factors. We compared HCC somatic mutations in patients of self-reported Asian American and EA from The Cancer Genome Atlas (TCGA), and assessed associations of tumor mutations with established HCC risk factors. Although the average mutation burden was similar, TP53 and RB1 were mutated at a much higher frequency in Asian Americans than in EAs (TP53: 43% vs. 21%; RB1: 19% vs. 2%). Three putative oncogenic genes, including TRPM3, SAGE1, and ADAMTS7, were mutated exclusively in Asians. In addition, VEGF binding pathway, a druggable target by tyrosine kinase inhibitors such as sorafenib, was mutated at a higher frequency among Asians (13% vs. 2%); while the negative regulation of IL17 production, involved in inflammation and autoimmunity, was mutated only in EAs (12% vs. 0). Accounting for HCC risk factors had little impact on any of the mutational differences. In conclusion, we demonstrated here mutational differences in important cancer genes and pathways between Asian and European ancestries. These differences may have implications for the prevention and treatment of HCC., Competing Interests: Dr. Biao Liu is a current employee of Genocea Biosciences, Inc., holds stock in the company, and holds a patent or intellectual property interest in the Scripps Research Institute. No other authors have any conflict of interests to disclose.

Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated increased interest recently as targets for newborn screening programs. Accurate epidemiological benchmarks are needed in the U.S. Age-specific mortality rates were estimated for Krabbe disease (KD) and nine related disorders. U.S. mortality records with E75.2 cause of death code during 1999-2004 were collected from 11 open record states. All E75.2 deaths in the United States were distributed into specific disease type based on proportions observed in these states. Yearly population sizes were obtained from the CDC and averaged. Mortality rates (per million individuals per year) by age group for the specific diseases were (for <5 or ≥5 years): Pelizaeus-Merzbacher (0.037/0.033); sudanophilic leukodystrophy (SLD) (0.037/0.004); Canavan (0.037/0.011), Alexander (0.147/0.022); Krabbe (0.994/0.007); metachromatic leukodystrophy (0.331/0.135); Fabry (0.000/0.124); Gaucher (0.221/0.073); Niemann-Pick (NP) (0.442/0.088); multiple sulfatase (0.000/0.004). This is the first report of mortality rates for the LD/LSD diseases in the U.S. Approximated birth prevalence rate for the early infantile Krabbe phenotype (onset 0-6 months) was based on the <5 year old mortality rate of one early infantile case per 244,000 births, which matches the 1 in 250,000 observed in the NYS newborn screening program as of 2011. It should be noted however that the NYS calculation refers only to the early infantile phenotype and does not include the majority of babies identified in the program with low GALC and two mutations who have remained clinically normal. It is presumed that most, if not all, will develop later onset forms of the disease, but this is by no means certain., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: The aim of this article was to obtain an overview of metastatic tumors to the oral and maxillofacial (OMF) region, especially the differences in the constituent ratios of primary cancers between the United States and China., Patients and Methods: Clinical findings of 19 cases encountered in West China Hospital of Stomatology were summarized and the English and Chinese literature were reviewed and analyzed. The main clinical features of OMF metastases were summarized, with an emphasis on primary cancers' constituents., Results: The lung, breast, kidney, liver, and prostate were the top 5 common primary sites of cancer. However, there was a significant difference in the primary cancers' constituents between United States and China (P < .001). The breast, kidney, prostate cancers, and melanoma of skin were more frequent primary cancers in United States than in China, whereas that of the lung, thyroid, liver, esophagus, and the stomach were more common in China than in United States. The proportions of the OMF metastatic lesions originating in the lung, kidney, liver, thyroid, and esophagus in all OMF metastatic tumors were higher than the corresponding primary cancers' prevalent proportions., Conclusions: The frequency of developing OMF metastasis is not always consistent with primary cancers' prevalence, which suggests that different cancers have different potentiality to develop OMF metastasis. Cancers of the kidney, liver, lung, thyroid, and esophagus were more likely to spread to the OMF region. In general screening of primary cancer, it would be helpful to take into account the metastatic potentiality of different cancers and primary cancers' prevalence in different countries in the case of occult primary.

Substantial racial differences in bone mass and bone loss rate have been reported, but the extent of the difference between native Chinese women and women of different races in the United States is not clear. We used a DXA bone densitometer to measure bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and volumetric BMD (vBMD) in different regions of the proximal femur in 3614 Chinese women aged 20 years and older. Regression models were chosen to best fit the changes of these parameters with increasing age. The values in their fitted curves were determined by the Cartesian coordinate numeration system. Subsequently, we compared these fitted curves to full-matched data of non-Hispanic black, non-Hispanic white, and Mexican American women reported by the third National Health and Nutrition Examination Survey (NHANES III). We found that all fitted curves of bone mass of non-Hispanic black women were significantly higher than those of Chinese, non-Hispanic white, and Mexican American women (P = 0.000). The BMD and BMC fitted curves in various regions of the hip for non-Hispanic blacks were 22%-28% and 26%-43% higher than those for Chinese women, 8.3%-13% and 7.9%-9.5% higher than those for non-Hispanic whites, and 8.8%-10% and 13%-19% higher than those for Mexican Americans, respectively. However, when the expression of difference was transformed from BMD to vBMD at the femoral neck, the difference between Chinese and non-Hispanic black women was reduced from 22% to 18% and that between Chinese and non-Hispanic white women from 7.4% to 0.8%, but the difference increased from 3.2% to 9.6% between non-Hispanic white and Mexican American women and from 13% to 17% between non-Hispanic white and non-Hispanic black women. By the age of 80 years, the accumulated bone loss rate in various regions of the proximal femur for Chinese, Mexican Americans, non-Hispanic whites, and non-Hispanic blacks were -38.9% +/- 1.8%, -34.4% +/- 3.1%, -27.8% +/- 5.9%, and -28.4% +/- 4.8%, respectively. In conclusion, bone mass in the proximal femur of native Chinese women is significantly lower, and the bone loss rate greater, than those of non-Asian women in the United States. At the femoral neck, the vBMD of Chinese women is similar to that of non-Hispanic white women.